THBS1

Fig1. Domain structure of TSP1 and its regional specific mimetic peptides and their function. (Bo Liu, 2024)

What is THBS1 Protein?

THBS1 gene (thrombospondin 1) is a protein coding gene which situated on the long arm of chromosome 15 at locus 15q14. The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. The THBS1 protein is consisted of 1170 amino acids and THBS1 molecular weight is approximately 129.4 kDa.

What is the Function of THBS1 Protein?

THBS1 is a multifunctional extracellular matrix protein and a member of the Thrombospondin family. It plays a role in a variety of biological processes, including cell adhesion, migration, proliferation, and regulation of cell survival. The role of THBS1 in the tumor microenvironment is multifaceted, it can inhibit angiogenesis, regulate anti-tumor immune response, stimulate tumor cell migration, and affect the activity of extracellular proteases and growth factors. In addition, THBS1 plays a regulatory role in tumor response to therapeutic radiation and chemotherapy.

Fig2. Effects of TSP1 and ligands in glucose metabolism and diabetes mellitus. (Linda S Gutierrez, 2021)

THBS1 Related Signaling Pathway

Thbs1-related signaling pathways are mainly involved in tumor development, cardiovascular stress response, tumor immune escape, and various cell signal transduction pathways. THBS1 is a member of the platelet reactive protein family, which plays an important role in several biological processes. During tumor development, THBS1 supports tumor cell adhesion and invasion by interacting with transforming growth factor β (TGF-β). At the same time, THBS1 also plays an important role in cardiovascular diseases, for example, under cardiac injury or stress response, THBS1 expression increases significantly and participates in the formation process of heart hypertrophy.

THBS1 Related Diseases

THBS1 is commonly associated with tumor development, cardiovascular disease, immunomodulatory and metabolic diseases. In nonalcoholic fatty liver disease, THBS1 serves as a novel biomarker whose levels are elevated in patients' serum and correlated with liver fat content. In addition, THBS1 expression in glioblastoma is associated with poorer patient outcomes and may influence the tumor microenvironment by regulating macrophage M0 infiltration. In laryngeal cancer, THBS1 is related to the migration, invasion and proliferation of tumor cells, and knocking out THBS1 can inhibit these abilities of tumor cells. In cardiovascular disease, THBS1 is involved in regulating angiogenesis and inflammatory responses, affecting the development of heart disease.

Bioapplications of THBS1

The use of THBS1 in a variety of diseases suggests that it is an important biomarker and therapeutic target. In nonalcoholic fatty liver disease, THBS1 serves as a novel biomarker, whose elevated serum levels are correlated with liver fat content, and exogenous recombinant THBS1 protein can inhibit liver lipid synthesis induced by high-fat diet in mice, thereby improving fatty liver symptoms. In addition, THBS1 is a potential therapeutic target in the treatment of colorectal cancer. These findings provide new strategies and ideas for the treatment of nonalcoholic fatty liver disease and colorectal cancer.

Case Study 1: Zhihao Wen, 2023

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSC. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC.

Fig1. WB was used to detect the activation of the PI3K/AKT signaling pathway after overexpression or knockdown of THBS1 in two OSCC cell lines.

Fig2. Quantitative analysis of the number of migrated and invasive cells.

Case Study 2: Yanzhang Li, 2013

In this study, researchers determined how TSP1 regulates macrophage function. Recombinant or purified platelet human TSP1 treatment stimulated tumor-necrosis factor (TNF)-α expression in bone marrow-derived macrophages in a time- and dose-dependent manner. Toll-like receptor 4 (TLR4) expression (at the mRNA and protein levels) and nuclear factor-kappaB (NF-κB) activity were also stimulated by TSP1 treatment. The TSP1-mediated increase in TNF-α production was abolished in TLR4-deficient macrophages, suggesting that TSP1 activates macrophages through a TLR4-dependent pathway. TSP1 also stimulated TLR4 activation in macrophages in vivo. Furthermore, TSP1-mediated macrophage activation was attenuated by using a peptide or an antibody to block the association between TSP1 and CD36. T

Fig3. TSP1 stimulated TNF-α expression and secretion in bone marrow-derived macrophages. BMDMs were treated with different concentrations of rhTSP1

Fig4. The NF-κB activity in whole-cell lysates was determined using an InstantOne ELISA kit. Human macrophages were treated with native TSP1 (10 μg/ml) for 24 h.

THBS1 has several biochemical functions, for example, calcium ion binding,collagen V binding,fibrinogen binding. Some of the functions are cooperated with other proteins, some of the functions could acted by THBS1 itself. We selected most functions THBS1 had, and list some proteins which have the same functions with THBS1. You can find most of the proteins on our site.

THBS1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with THBS1 here. Most of them are supplied by our site. Hope this information will be useful for your research of THBS1.

PCOLCE;TGFB1;PLEK;chondroitin_sulfate;dermatan_sulfate;heparin;heparan_sulfate;collagen_i_human;collagen_xi_human;collagen_vi_human;FN1;APP;Col11a1;BGN;TGM2